We have shown that the E1A gene of nonocogenic Ad2 and Ad5 induces susceptibility to NK cell and macrophage mediated lysis in transformed rodent cells and that the expression of high levels of susceptibility correlates with transformed cell tumor inducing capacity. Adaptation of Ad2 transformed cells to produce tumors in tumor resistant syngeneic adult hamsters by serial passage in newborns results in cells that are resistant to NK and macrophage killing and whose E1A gene function is disrupted to the extent that these cells will not support replication of Ad2 E1A mutants. We have also found that Ad12 transformed hamsters cells that have low levels of class I MHC antigens on their surfaces are generally nontumorigenic in allogenic hamsters and mice and are highly immunogenic in bioassays for CTL mediated detection of Ad12 transplantation antigens. Our Ad12 transformed BALB/c mouse cells (haplotype H-2d) produce tumors in BALB/c and DBA-2mice (haplotype H-2d) but fail to produce tumors in mice with recombinant haplotypes (H2-kd, H-2Db, H-2Lb or H-2Kb, H-2Dd, H-2Ld); thus these cells can be rejected as allografts by H-2 divergent mice in spite of their low levels of class I MHC antigen expression. Several Ad5 transformed BALB/c mouse cell lines that we have developed express peculiar patterns of expression of the Ad5 genome. Some of the cells retain Ad5 DNA, express Ad5 mRNA and Ad5 early proteins. Others retain Ad5 DNA but fail to express Ad5 mNRNA. One line that is morphologically similar to the others contains no Ad5 DNA. These data suggest that persistance of the Ad5 genome and expression of viral protein may not be essential to maintaining the neoplastic phenotype of Ad5 transformed BALB/c mouse cells.